CD 95 expression in traumatic proliferative vitreoretinopathy: a target for the induction of apoptosis

Apoptotic cell death is a central mechanism underlying growth regulation in normal and pathologic neoplastic and nonneoplastic tissue formation. Apoptosis has also been detected in traction membranes of patients with proliferative vitreoretinopathy (PVR). Herein we report that CD 95 (Fas/APO-1), the cell-surface receptor for a potent proapoptotic cytokine, the CD 95 ligand, is expressed in traction membranes of patients with traumatic PVR. Retinal pigment epithelial (RPE) cells, which are thought to contribute to traction membrane formation, express CD 95 in vitro. However, these cells are resistant to CD 95 antibody-induced apoptosis, presumably because they synthesize cytoprotective proteins, which interfere with the CD 95-dependent killing cascade. Coexposure to inhibitors of RNA or protein synthesis sensitizes human RPE cells for CD 95-mediated apoptosis. In contrast, these agents have little effect on the resistance of these cells to tumor necrosis factor-alpha(TNF-alpha). Pre-exposure to TNF-alpha augments CD 95-mediated killing but not its own toxicity in the presence of inhibitors of RNA and protein synthesis. Preexposure to cycloheximide does not abrogate CD 95-mediated apoptosis, suggesting that labile, short-lived proteins do not mediate the cytotoxic effects of CD 95 antibodies. Taken together, our data indicate that immune-mediated CD 95-dependent killing of proliferating cells in vitreoretinal traction membranes might occur in vivo and could possibly be enhanced using novel approaches of immunopharmacotherapy.